When the 2015/2016 Zika virus epidemic swept through the Americas and several islands in
the Pacific and Southeast Asia, researchers
were urged to focus their efforts on developing treatments and vaccines to combat
the virus’ effects.

A team of researchers from the Center
for Genome Architecture at Baylor College
of Medicine coincidentally had crucial
but fragmented pieces of relevant data
from previous research that could greatly
impact this effort. Using a 3-D genome
assembly approach referred to as HI-C,
the team was able to quickly assemble the
1.2 billion letter genome of Aedes aegypti,
the Zika-carrying mosquito, producing
the first end-to-end assembly of each of its
three chromosomes.

“When the Aedes mosquito cameinto the spotlight in relation to the Zikaepidemic, we found ourselves sitting on abunch of relevant data and proof-of-prin-ciple work,” said Olga Dudchenko, a post-doctoral fellow at The Center for GenomeArchitecture. “The situation prompted usto polish our methods and share the dataThe development provides a much-need-ed boost to research and treatment optionsfor the Zika virus by identifying vulnera-bilities in the mosquito that the virus usesto spread.

With the success of assembling the
Aedes genome, the Baylor team has also
shown that the 3-D assembly technique
can be an important tool for similar
outbreaks in the future, and could also aid
in personalized care for human patients
suffering from a variety of diseases.

Timeline

Erez Lieberman Aiden, Director of the
Center for Genome Architecture, originally
proposed the general idea of 3-D assembly
in 2009.

Lieberman Aiden and colleagues first
tested their technique in 2013 by sequencing a human genome, and comparing the
data to that made available by the Human
Genome Project.

The team found their assembly correlated with the reference data from the Human
Genome Project with 99 percent accuracy,
validating the method. However, the 3-D
assembly method produced similar results
in a fraction of the time, and at significantly less cost.

They then switched their focus toward
the Aedes aegypti mosquito, which is
responsible for the spread of not only Zika
virus, but dengue, chikungunya and yellow
fever. When the Zika outbreak began to
become a global health threat, the team
knew they could piece together information they acquired from previous research
to create a clear, cohesive picture of the
mosquito’s genome.

3-D assembly allowed the team to create
the 1.2 billion-letter genome of the mosquito for about $10,000—a price comparable
to that of an MRI scan.

The third phase of their research included assembling the genome of the Culex
quinquefasciatus mosquito, a carrier of
West Nile virus.

“Culex is another important genome tohave since it is responsible for transmit-ting so many diseases,” said LiebermanAiden. “Still, trying to guess what genomeis going to be critical ahead of time is nota good plan. Instead, we need to be ableto respond quickly to unexpected events.Whether it is a patient with a medicalemergency or the outbreak of an epidemic,these methods will allow us to assemble denovo genomes in days, instead of years.”For the Culex sequence, the researcherscarried out their work with IBM’s VOL-TRON—a high performance computing(HPC) system. VOLTRON is based on thecompany’s Power Systems platform, whichprovides scalable HPC capabilities neces-sary to accommodate a broad spectrum ofdata-enabled research activities. The PowerSystems platform has also been selectedfor use by the Department of Energy’s OakAssembling Genomes from Scratch,

at a Fraction of the Cost

3-D genome assembly technology is changing how scientists createspecies’ genomes, by speeding up the process and doing it at a muchlower cost than previous methods.

by Lauren Scrudato, Managing Editor

The Aedes aegypti mosquito is a primary carrier
of the Zika virus. Photo: James Gathany, CDC